Tirzepatide and cardiovascular outcomes: A narrative review of mechanisms, efficacy and implications for heart failure management

Authors

Hamza A. Abdul-Hafez, Department of Medicine, An Najah National University, Nablus, Palestine.
Ameer Awashra, Department of Medicine, An Najah National University, Nablus, Palestine.
Sosana Bdir, Department of Medicine, An Najah National University, Nablus, Palestine.
Sarah Saife, Department of Medicine, An Najah National University, Nablus, Palestine.
Qasem Salah, Department of Medicine, An Najah National University, Nablus, Palestine.
Mohammed Barbarawi, Department of Medicine, An Najah National University, Nablus, Palestine.
Thabet Swaileh, Department of Medicine, An Najah National University, Nablus, Palestine.
Ahmed Emara, Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Mohamed S. Elgendy, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt.
Abdalhakim Shubietah, Advocate Health - MidwestFollow

Recommended Citation

Abdul-Hafez HA, Awashra A, Bdir S, et al. Tirzepatide and Cardiovascular Outcomes: A Narrative Review of Mechanisms, Efficacy and Implications for Heart Failure Management. Endocrinol Diabetes Metab. 2026;9(1):e70152. doi:10.1002/edm2.70152

Affiliations

Advocate Illinois Masonic Medical Center

Abstract

Background: Tirzepatide, a dual GIP/GLP-1 receptor agonist, offers a novel cardiometabolic strategy beyond glycemic control with important implications for heart failure care. By producing potent, sustained weight reduction and favourable changes in lipids, blood pressure, systemic inflammation and endothelial biology, tirzepatide targets central pathophysiologic drivers of obesity-related HFpEF.

Methods: We conducted this review to synthesise current evidence on the mechanisms, clinical efficacy and therapeutic implications of tirzepatide for heart failure management, with emphasis on obesity-related HFpEF, cardiorenal effects and safety considerations. Randomised clinical programmes and the SUMMIT outcomes trial have demonstrated symptomatic and functional improvements, reverse cardiac remodelling on imaging, reduced circulating markers of myocardial stress and fewer worsening heart-failure events versus placebo, alongside signals of renal stabilisation.

Results: The tolerability profile aligns with the GLP-1 class, with gastrointestinal events predominating and a low risk of clinically important hypoglycemia; biliary events may be more likely at higher doses, while pancreatitis risk has not been clearly elevated. Data in HFrEF remain limited and caution is advised given prior mixed results with incretin therapies and theoretical concerns about rapid weight loss in advanced systolic failure.

Conclusion: This review integrates mechanistic insights and contemporary trial evidence to clarify how dual incretin agonism may modify the trajectory of obesity-driven heart failure, to inform multidisciplinary clinical decision making, and to highlight key unanswered questions and research priorities needed to define tirzepatide's full role in heart failure management.

Type

Article

PubMed ID

41566974